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Orthotopic Implantation and Peripheral Immune Cell Monitoring in the II-45 Syngeneic Rat Mesothelioma Model
Published on: October 2, 2015
Immunological monitoring of cancer vaccine therapy
Dirk Nagorsen1, Carmen Scheibenbogen, Eckhard Thiel
1Charité, Campus Benjamin Franklin, Medizinische Klinik III, Hindenburgdamm 30, 12200 Berlin, Germany. dirk.nagorsen@charite.de
Abstract:
Immunological treatment of malignant diseases in humans aiming at the induction and proliferation of antigen-specific T cells has made rapid progress in recent years. A growing number of tumour-associated antigens, potentially synergistic combinations with adjuvants, and various routes of application provide new opportunities for cancer vaccination. Therefore, a highly accurate assessment of vaccine-induced T cell responses is required. Three T cell assays (tetramers, intracellular cytokine flow cytometry and ELISPOT assay) have emerged as first-line methods for monitoring T cell induction during vaccination. These assays are relatively easy to perform, reliable, sensitive and allow an ex vivo T cell analysis at the single cell level. Although at this stage assays are not a defined surrogate marker for clinical efficacy, they already provide information concerning the immunological potency of a given vaccine. In particular, comparing immune responses under various treatment conditions will help to develop more clinically efficient tumour vaccination. Novel assays, such as CD107 staining, human leukocyte antigen/green fluorescent protein-antigen-presenting cells or microarrays, and assays determining functions, such as proliferation assays, are beginning to complement first-line monitoring assays.
Insights
Cancer vaccines aim to boost T cell responses for treating malignant diseases. Current assays like tetramers, intracellular cytokine flow cytometry, and ELISPOT enable accurate monitoring of these crucial immune cells.
Area of Science:
- Immunology
- Oncology
- Vaccinology
Background:
- Recent advancements in cancer immunotherapy focus on inducing antigen-specific T cells.
- Cancer vaccination strategies are expanding with new tumor antigens, adjuvants, and delivery methods.
- Accurate assessment of vaccine-induced T cell responses is critical for therapeutic development.
Purpose of the Study:
- To review current methods for assessing T cell responses in cancer vaccination.
- To highlight the importance of reliable T cell monitoring for vaccine efficacy.
- To discuss emerging assays that complement established methods.
Main Methods:
- Tetramer staining for direct visualization of antigen-specific T cells.
- Intracellular cytokine flow cytometry to detect cytokine production by T cells.
- ELISPOT assay for quantifying cytokine-secreting T cells at the single-cell level.
Main Results:
- Tetramers, intracellular cytokine flow cytometry, and ELISPOT are established first-line assays for monitoring T cell induction.
- These assays offer reliable, sensitive, ex vivo, single-cell analysis of T cell responses.
- While not direct markers of clinical efficacy, they provide crucial data on vaccine immunological potency.
Conclusions:
- Established T cell assays are essential for evaluating the immunological potency of cancer vaccines.
- Comparative analysis of immune responses using these assays aids in optimizing tumor vaccination strategies.
- Novel assays are emerging to provide a more comprehensive understanding of vaccine-induced T cell functions.
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